It has been discovered that polarized inert noble gases can produce improved MRI images of certain areas and regions of the body that have heretofore produced less than satisfactory images in this modality. Polarized helium-3 (“3He”) and xenon-129 (“129Xe”) have been found to be particularly suited for this purpose. Unfortunately, as will be discussed further below, the polarized state of the gases is sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly.
Polarizers are used to produce and accumulate hyperpolarized noble gases. Polarizers artificially enhance the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the MRI signal intensity, thereby providing better images or signals of the substance in the body. See U.S. Pat. Nos. 5,545,396; 5,642,625; 5,809,801; 6,079,213, and 6,295,834; the disclosures of these patents are hereby incorporated by reference herein as if recited in full herein.
In order to produce the hyperpolarized gas, the noble gas can be blended with optically pumped alkali metal vapors such as rubidium (“Rb”). These optically pumped metal atoms collide with the noble gas atoms and hyperpolarize the noble gas nuclei through a phenomenon known as “spin-exchange.” The “optical pumping” of the alkali metal vapor is produced by irradiating the alkali-metal vapor with circularly polarized light at the wavelength of the first principal resonance for the alkali metal (e.g., 795 nm for Rb). Generally stated, the ground state atoms become excited, then subsequently decay back to the ground state. Under a modest magnetic field (about 10 Gauss), the cycling of atoms between the ground and excited states can yield nearly 100% polarization of the atoms in a few microseconds. This polarization is generally carried by the lone valence electron characteristics of the alkali metal. In the presence of non-zero nuclear spin noble gases, the alkali-metal vapor atoms can collide with the noble gas atoms in a manner in which the polarization of the valence electrons is transferred to the noble-gas nuclei through a mutual spin flip “spin-exchange.”
The alkali metal is removed from the hyperpolarized gas prior to introduction into a patient to form a non-toxic and/or sterile composition. Other polarization techniques not employing alkali metal spin exchange can also be employed as is known to those of skill in the art.
Unfortunately, the hyperpolarized state of the gas can deteriorate or decay relatively quickly and therefore must be handled, collected, transported, and stored carefully. The “T1” decay constant associated with the hyperpolarized gas' longitudinal relaxation time is often used to describe the length of time it takes a gas sample to depolarize in a given situation, generally by about 36.7%. The handling of the hyperpolarized gas is critical because of the sensitivity of the hyperpolarized state to environmental and handling factors and the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, i.e., delivery to a patient for imaging. Processing, transporting, and storing the hyperpolarized gases—as well as delivery of the gas to the patient or end user—can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic gradients, contact-induced relaxation, paramagnetic impurities, and the like.
The actual polarization level of the gas can be measured using a polarization measurement station 12 as depicted in FIGS. 1 and 2. Polarization measurement station 12 includes an NMR pickup coil 14 held by a planar substrate 16 horizontally spanning the axis of a first and second annular coil form 18 and 20. Pickup coil 14 is connected to an NMR pickup circuit 15. Coil forms 18 and 20 are about 30 inches in diameter while pickup coil 14 measures about one inch in diameter. When measuring the polarization of a gas sample, the polarized gas sample 11 is positioned upon substrate 16 over pickup coil 14. Polarization measurement station 12 may be calibrated before leaving its manufacture facility through comparison with thermally polarized H2O in a high field NMR magnet.
However, there is no method for checking that calibration while the polarization measurement station 12 is in the field. The high field NMR magnet and spectrometer used in the factory is not readily portable, and there is no calibrated method of measuring 3He polarization in the field other than with the polarimetry station itself. There is therefore a need for a transfer standard, analagous to a set of weights for a scale, to check the calibration of devices designed to measure the polarization of a hyperpolarized gas. An ideal transfer standard, for example, would be a sample of a hyperpolarized gas having a fixed level of polarization which does not decay with time so as to appear to polarization measurement station 12 like a perpetually hyperpolarized bag of 3 He. 